Jessica Quintin

Website: https://research.pasteur.fr/en/team/immunology-of-fungal-infections/
ORCID: 0000-0002-1589-9034
Twitter: @JessicaQuintin

1) Research in our lab strives to understand the mechanisms of the host immune response to human fungal pathogens, such as Candida albicans, Aspergillus fumigatus and Cryptococcus neoformans.

Superficial fungal infections are unfortunately very common, with most people experiencing some during their lifetimes, but are generally easy to cure. In contrast, invasive fungal diseases are associated with very high morbidity and mortality rates.  Over 1.7 million people die every year due to invasive fungal infections despite the discovery of novel and more potent antifungal drugs against the major fungal pathogens (Candida, Aspergillus, and Cryptococcus spp.).

Systemic candidiasis is the third most common cause of mortality in hospital infections. Patients with acquired innate cells (especially neutrophils) defects are at height risk of developing invasive candidiasis with poor outcome. Mortality reaches the unacceptable rate of 40%, despite the antifungal therapies.

The combination of antifungal drugs with stimulation/modulation of the host innate immune system could represent a potent approach to improve this outcome. It is therefore crucial to better understand the host-pathogen interactions and the host innate immune mechanisms to fungal infections.

Combining human, murine, in vitro and in vivo experimentation models we are deciphering the immunological modulation of the innate immune response triggered by fungal infections and the associated innate immune memory.

On the one hand we unravel the molecular mechanisms and physiological characteristics associated with the modulation of the innate immune memory. On the other hand we decipher the fungal associated molecules and factors that triggers such modifications of the innate immune system. As such we and others have shown that, in vitro, innate immune cells can be “trained” by the fungal polysaccharide beta-glucan to respond more potently to microbial stimuli, however its potential in vivo mechanisms against fungal infections are unknown. In addition we recently uncover that the regulation of innate cells by beta-glucan is highly dependent on the environment and that beta-glucan treatment does not always enhance macrophage function. We showed that within an inflammatory context, beta-glucan treatment can have a repressive role, even in the context of autoinflammatory disorders.

2) We have strong expertise in investigating human primary immune cells for their immune status towards infection and inflammatory responses (ranging from phagocytosis, cytokines expression to onflamsomme activation towards fungal but also bacterial challenges). We also master mouse models of invasive fungal infection (such as candidiasis) and the study of the host immune responses systemically and locally in the organs.

Top 5 publications

1- Corbellini Piffer A, Camilli G, Bohm M, Lavenir R, Quintin J#, β-glucan-induced innate immune memory distinctively affect macrophage activation in response to differential environmental cues. bioRxiv 2021.08.30.458241; doi: https://doi.org/10.1101/2021.08.30.458241

2- Camilli G, Bohm M, Corbellini Piffer A, Lavenir R, Williams DL Neven B, Grateau G, Georgin-Lavialle S, Quintin J#, β-Glucan-induced reprogramming of human macrophages inhibits NLRP3 inflammasome activation in cryopyrinopathies J Clin Invest. 2020 Sep 1;130(9):4561-4573. doi: 10.1172/JCI134778.

3- Santecchia I, Vernel-Pauillac F, Rasid O, Quintin J, Gomes-Solecki M, Boneca IG, and Werts C. Innate immune memory through TLR2 and NOD2 contributes to the control of Leptospira interrogans infection. PLoS Pathog. 2019 May 20;15(5):e1007811. doi: 10.1371/journal.ppat.1007811. eCollection 2019 May.

4- Quintin J# Fungal mediated innate immune memory, what have we learned? Semin Cell Dev Biol. 2019 May 30. pii: S1084-9521(17)30379-8. doi: 10.1016/j.semcdb.2018.05.023. [Epub ahead of print] Review.

5- Camilli G, Eren E, Williams DL, Aimanianda V, Meunier E, Quintin J#. Impaired phagocytosis directs human monocyte activation in response to fungal derived β-glucan particles. Eur J Immunol. 2018 Jan 5. doi: 10.1002/eji.201747224.

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